This program project proposes to investigate the nephritogenic and transplantation activities of the streptococcal membrane and soluble fractions derived from it. Three laboratories representing a broad interdisciplinary spectrum of scientific backgrounds are involved in the experimental work proposed; each of these laboratories has unique talents and personnel which complement each other in the fulfillment of the research protocols described in this application. Duplication of such expertise and facilities in any one laboratory would be costly and time consuming, thus making the proposed approach a logical one. It is our intent to utilize soluble materials from the streptococcal membrane for inducing glomerulonephritis and to evlauate the relationships of such materials to the HL-A system. It is intended to chemically characterize the effector molecule(s) and to alter it so that it may be further explored in these experimental parameters. As a consequence of such studies it is anticipated that the question of whether a single effector molecule contains biologic activity both as a nephritogen and as a transplantation antigen may be resolved. This approach may provide a more definitive insight into the membrane chemistry of human glomerular basement membrane, streptococcal protoplasmic membrane and human lymphocyte membrane, with a better understanding of possible biological relationships between these entities.